The localization of aldosterone-producing adenoma on computed tomography--a comparative study with adrenal scintigraphy and plasma aldosterone concentration in the adrenal or renal vein

The evaluation of computed tomography (CT) for detecting aldosterone-producing adenoma in primary aldosteronism was performed by comparison with adrenal scintiscan; determination of aldosterone in adrenal or renal veins, retroperitoneal pneumography and adrenal venography was reliable for diagnosis of adrenal tumors in pheochromocytoma or Cushing's syndrome, but not so effective for small adenoma of primary aldosteronism. An abdominal CT scan was performed on six patients with primary aldosteronism, one with idiopathic hyperaldosteronism and one with glucocorticoid responsive hyperaldosteronism; in an attempt to evaluate the utility of this noninvasive procedure. Diagnosis of hyperaldosteronism was made by demonstrating the elevated plasma aldosterone concentration and aldosterone secretion rate, normal excretion rate of urinary 17-OHCS and 17-KS, and low plasma renin activity. The CT scan correctly predicted unilateral adrenal adenoma in all the patients with primary aldosteronism of which the findings were identical to those demonstrated by surgery. The diameter of these tumors ranged from 10 X 7 X 6 to 19 X 17 X 14 mm. Also the CT scan in idiopathic hyperaldosteronism and glucocorticoid responsive hyperaldosteronism showed bilateral adrenal hyperplasia and bilateral normal adrenal glands, respectively. The pathological findings in these two cases disclosed the adrenal hyperplasia of zona glomerulosa and adrenal hyperplasia of zona subglomerulosa accompanied by a normal thickness of the adrenal gland, respectively. The precision of the CT scan, adrenal scintigraphy and determination of plasma aldosterone in the adrenal or renal veins were almost equal to the diagnosis of the localization of adrenal adenoma. It is concluded that the CT scan is a noninvasive and most useful method for the localization of aldosterone-producing adenoma and helpful in distinguishing adrenal adenoma from adrenal hyperplasia.     

Relative value of computed tomography scanning and venous sampling in establishing the cause of primary hyperaldosteronism

The purpose of this study was to evaluate the relative merits of the postural stimulation test, adrenal computed tomography (CT) and venous sampling in the differential diagnosis of patients presenting with primary hyperaldosteronism. The records of 20 patients presenting with primary hyperaldosteronism were reviewed retrospectively. There were 15 patients with a unilateral aldosterone-producing adenoma (APA), four patients with idiopathic hyperaldosteronism (IHA) and one patient with primary adrenal hyperplasia (PAH). The postural stimulation test was based on measurements of plasma aldosterone and renin activity at 08.00 h and at noon after 4 h of ambulation. The CT scans of the adrenals were reviewed by a single radiologist. Bilateral venous sampling of adrenal veins was attempted in all patients and blood collected for aldosterone and cortisol assay. Plasma aldosterone concentration increased after 4 h of standing in all cases of hyperplasia but was also demonstrated in 10/15 patients with a surgically-proven APA. If one defines a significant postural rise as being greater than 30%, then 8/15 patients with APA can be considered as being posturally responsive. Computed tomography scanning correctly identified all 15 cases of APA and also classified correctly the remaining five cases of hyperplasia (four cases of IHA and one case of PAH). Venous sampling failed technically in 4/15 cases of APA and in one case of IHA: a total of 5/20 (25%,). A correct diagnosis of APA or IHA was established in all the remaining cases. However, the one case of PAH was treated successfully by adrenalectomy following venous sampling, which suggested a unilateral adrenal lesion: this one result was the only instance where venous sampling altered clinical decision-making. Computed tomography scanning may be used alone to confirm the cause of hyperaldosteronism where postural studies suggest an adrenal adenoma, and such patients may be considered for early surgery. Venous catheterization studies are not necessary routinely. but may still be useful in selected patients, particularly when CT scanning shows no clear lesion.     

Idiopathic primary hyperaldosteronism: significance of functional diagnosis

Primary aldosteronism is a rare cause of hypertension caused by increased aldosterone secretion. The two essential stimuli for aldosterone production, potassium and angiotensin II, tend to be low. At a time when imaging procedures are becoming more common, more patients are being found with adrenal masses, and patients with incidentalomas and low renin hypertension could be considered as candidates for surgery. Apart from an appropriate work-up for the diagnosis of primary aldosteronism, the differential diagnosis between unilateral adenoma and idiopathic ("hyperplasia") hyperaldosteronism is relevant for the choice of therapy. Based on data from the literature and four patients we observed as outpatients in 1997, we suggest that a properly conducted and carefully interpreted postural stimulation test can be useful in identifying patients who are successfully treated by drugs.     

Pre-operative localization of aldosterone-secreting adrenal adenomas

Techniques for pro-operative localization of aldosterone-secreting adrenal adenomas were studied in thirty-seven patients, each with hypertension and biochemical evidence of primary hyperaldosteronism and each later having adrenal surgery (thirty-two adenomas, five bilateral hyperplasia). Bilateral adrenal vein catheterization was attempted in all cases; it was successful on the left side in all patients and in 92% of cases on the right. Adrenal vein plasma samples were obtained from the left side in 92% and from the right in 73% of cases. Adrenal vein plasma aldosterone measurements correctly indicated the presence of tumour in twenty-eight cases but falsely predicted unilateral adenoma in two cases of bilateral adrenal hyperplasia. Adrenal venography also correctly predicted unilateral adrenal adenomas in twenty-six cases but falsely suggested the presence of tumour in three cases of bilateral adrenal hyperplasia. Computed tomography (CT) was used in the last eight cases. In seven instances the predictions (six adenomas, one bilateral adrenal hyperplasia) were confirmed at surgery. However, the remaining patient harboured an adenoma 20 mm in diameter which was not detected by CT although diagnosed both by adrenal venography and adrenal vein aldosterone measurements. Ultrasound detected adenoma in only three of twenty-two cases examined. Although further comparative studies of the type described here are required, the results of computed tomography are promising and suggest that this non-invasive technique might well become the first choice procedure in localizing aldosterone-secreting adenomas.     

The influence of dose and dose rate on the incidence of neoplastic disease in RFM mice after neutron irradiation

The effect of circadian rhythm and alterations in posture on plasma aldosterone concentration was studied in 13 patients with primary aldosteronism (six adenoma, five idiopathic hyperplasia, two carcinoma) to define the regulatory mechanism in each of these pathologic subtypes. Blood samples for aldosterone, cortisol, renin, and potassium concentrations were obtained every 4 h during prolonged recumbency (32 h) and upright posture (16 h). During recumbency, aldosterone and cortisol followed a normal circadian pattern in patients with adenoma and hyperplasia, with peak values at 0400-0800 h and the nadir at 1600-2400 h. Normalized aldosterone and cortisol values correlated significantly in both groups (adenoma r=+0.66, P less than 0.001; hyperplasia r=+0.42, P less than 0.01). With upright posture, aldosterone levels declined parallel to the normal circadian fall in cortisol in patients with adenoma (r=+0.68, P less than 0.001); whereas aldosterone levels increased in patients with hyperplasia parallel to small increments in renin (r=+0.65, P less than 0.001) and potassium (r=+0.64, P less than 0.001). During the administration of dexamethasone, aldosterone no longer correlated with cortisol in patients with adenoma but continued to correlate with renin during upright studies in patients with hyperplasia (r=+0.77, P less than 0.01). Aldosterone circadian rhythm was abnormal in patients with carcinoma and no effect of posture was noted. Unilateral adrenalectomy restored the normal postural relationship in four patients with adenoma. These studies suggest that aldosterone secretion is under continuous ACTH control regardless of posture in patients with adenoma, whereas persistent adrenal responsiveness to small increments in renin and/or potassium mediate the postural increase in plasma aldosterone in patients with hyperplasia. True adrenal autonomy occurs only in patients with adrenal carcinoma and when ACTH is suppressed in those with adenoma.     

Differential diagnosis in primary aldosteronism

The diagnosis of primary aldosteronism (PA) is based on the finding of the combination of elevated urinary and/or plasma aldosterone and suppressed renin activity in patients with hypertension and hypokalemia. However, PA consists of a number of subsets, and diagnostic criteria for a correct identification of surgically remediable forms are of great interest. The methods and the results concerning our series of 113 patients with PA are presented in this review. Aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were the most frequent forms, 51 and 44%, respectively. They had similar blood pressure levels, but hypokalemia was most frequently found in APA. Urinary and upright plasma aldosterone were similar, but supine plasma aldosterone was lower in IHA. Plasma aldosterone response to upright posture and angiotensin II infusion was absent in most cases of APA and present in IHA, but occasionally renin-responsive adenoma were found. Captopril failed to decrease plasma aldosterone in most patients with APA, and in a subgroup of patients with IHA. Patients with adenoma also had higher values of the aldosterone precursor 18-hydroxy-corticosterone, and of atrial natriuretic peptide, probably as a consequence of a greater degree of volume expansion. Among morphological studies, CT scan and adrenal radiocholesterol scintiscan provided similar results (85% accuracy): adrenal veins catheterization clarified almost all the remaining cases. Among the subsets of PA, 3 familiar cases of dexamethasone-suppressible hyperaldosteronism were recognized, with characteristically high levels of aldosterone, 18-hydroxy-corticosterone, 18-hydroxy-cortisol and 18-oxo-cortisol, due to the genetic abnormalities of the 11-18 hydroxylase system. Isolated cases of primary adrenal hyperplasia (with all functional tests resulting compatible with APA, but no tumour at surgery) and aldosterone producing carcinoma (1 case) have also been reported in the present study.     

Radiology in primary hyperaldosteronism

Autonomous hypersecretion of aldosterone (primary hyperaldosteronism) is caused by either hyperplasia (usually bilateral) or an adenoma (frequently unilateral) of the adrenal cortex. Systemic hypertension due to an aldosteronoma is a potentially curable condition through surgical extirpation of the offending organ. In our experience with 37 patients clinically suspected to have primary hyperaldosteronism, radiological methods contributed significantly in preoperative diagnosis. These included (1) selective bilateral adrenal vein catheterization and blood sample collection, (2) adrenal venography, and (3) radioisotope adrenal scan. Unilateral hyperfunction could be accurately detected by the aldosterone assays from the collected samples. When adrenal venography was technically satisfactory, a nodule or aggregate of nodules measuring at least 7 mm and located on the margin of the gland or 1.5 cm or more in diameter when located in the center of the gland were readily identified. Enlarged adrenal gland on venography, in itself, was not a dependable index of a hyperfunctioning gland. Presence of a higher uptake on one side on the radioisotope adrenal scan did not always indicate the hyperfunctioning gland, but lack of lateralization of adrenal hyperfunction was more accurately predicted on the radioisotope scan than by venography. Four histopathological patterns were recognized in the surgically removed adrenal glands, but no correlation between these patterns and clinical behavior or postoperative course was found.     

Latent tetany associated with the hypokalaemia of Conn''s syndrome

We describe the case of an asymptomatic patient with primary hyperaldosteronism, who was diagnosed fortuitously following the demonstration of a positive Trousseau's sign during routine blood pressure assessment. Further investigations revealed that the carpal spasm was due solely to the associated profound hypokalaemia.     

Mineralocorticoid syndromes and hypertension

Mineralocorticoids are out of the causes of secondary hypertension. Excess production of mineralocorticoids induces sodium and fluid retention, loss of potassium and metabolic alcalosis. The diagnosis of mineralocorticoid syndromes depends on the interpretation of the functional status of the renin-mineralocorticoid-system, which is in part responsible for the maintenance of normal blood pressure. The classical representative of this group is the syndrome of primary aldosteronism. Causes of mineralocorticoid syndromes associated with hypertension are: 1. autonomous production of mineralo-corticoids by an adrenal adenoma or by idiopathic bilateral adrenal hyperplasia; 2. deficiency of adrenal 17-alpha-hydroxylase or of 11-beta-hydroxylase; 3. secondary aldosteronism associated with primary reninism, or renal arterial stenosis; and 4. pseudo aldosteronism due to excessive ingestion of licorice. Malign or essential hypertension may also often be followed by secondary aldosteronism.     

Adrenomedullary hyperplasia associated with cortisol producing adenoma

We report a case of a 58-year-old man with adrenal medullary hyperplasia associated with cortisol producing adenoma. Preoperative examination showed both adrenocortical and adrenomedullary hyperfunction. No Cushingoid sign was present and pheochromocytoma-like symptoms were predominant. Abdominal computerized tomography revealed a left adrenal tumor stained by contrast medium. Histologically, the adrenal tumor was found to be a cortical adenoma, and medullary hyperplasia was observed in the remaining parenchyma.     

Conn syndrome: 14 year's experience from two European centres

OBJECTIVE: To evaluate the long term results of adrenalectomy for primary hyperaldosteronism. DESIGN: Multicentre retrospective cohort study. SETTING: Two university hospitals, UK and Italy. SUBJECTS: 55 patients who presented with a mean (SD) preoperative blood pressure of 181/110 (21/10) mmHg and a mean (SD) potassium of 2.8 (0.4) mmol/L (range 1.6-4) during the period October 1978 to October 1992. INTERVENTIONS: Unilateral adrenalectomy, usually by the extraperitoneal approach. Adrenalectomy was total in all but nine cases. MAIN OUTCOME MEASURES: Accuracy of preoperative investigations for the diagnosis and localisation of the lesions, histology, morbidity and mortality, long term outcome (mean follow up 8.8 years). RESULTS: Computed tomography gave a diagnostic accuracy for unilateral lesions of 88%, the postural stimulation test 80%, norcholesterol scintigraphy 84%, and ultrasonography 57%. Histological examination showed carcinoma (n = 1), diffuse hyperplasia (n = 2), nodular hyperplasia (n = 11) including 5 with macronodular hyperplasia, double adenoma (n = 1) and single adenoma (n = 40). No patient died, and 10 developed minor complications. At the latest follow-up 44/52 patients with benign unilateral lesions (85%) have been cured by adrenalectomy. CONCLUSIONS: Our results confirm the safety of the extraperitoneal approach, and suggest that the improvement in the accuracy of preoperative investigations has allowed a careful selection of patients with the consequent amelioration of the long term outcome of surgery for Conn's syndrome. As laparoscopic adrenalectomy is currently advocated as the operation of choice for surgically-remediable mineralocorticoid excess, its long term results will have to be comparable with these standards.     

A case report of obstructive sleep apnea syndrome associated with primary aldosteronism

A 60-year-old obese woman was admitted for evaluation of excessive daytime sleepiness, loud snoring, cyanosis, systemic edema, hypertension and diabetes mellitus. Laboratory examination showed severe hypoxemia, hypercapnea, metabolic alkalosis, hypokalemia and hyperaldosteronism. CT scan showed a left adrenal tumor. A diagnosis of obstructive sleep apnea syndrome associated with primary aldosteronism was established. Metabolic alkalosis, hypokalemia and sodium retention due to hyperaldosteronism were thought to be factors exacerbating her sleep apnea.     

Aldosterone excess: a rare non-nephrophathic cause of hypertension in type I diabetes

The aetiology of hypertension in type 1 diabetes is commonly due to the presence of diabetic nephrology. A rare case of hypertension in a patient with type 1 diabetes and no proteinuria is reported, where the investigation of borderline hypokalaemia allowed us to make a diagnosis of hyperaldosteronism due to bilateral adrenocortical hyperplasia. Secondary causes of hypertension should always be considered in all diabetic patients, particularly in the absence of clinical proteinuria.     

Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene

Familial hyperaldosteronism type II (FH-II) is characterized by autosomal dominant inheritance and hypersecretion of aldosterone due to adrenocortical hyperplasia or an aldosterone-producing adenoma; unlike FH type I (FH-I), hyperaldosteronism in FH-II is not suppressible by dexamethasone. Of a total of 17 FH-II families with 44 affected members, we studied a large kindred with 7 affected members that was informative for linkage analysis. Family members were screened with the aldosterone/PRA ratio test; patients with aldosterone/PRA ratio greater than 25 underwent fludrocortisone/salt suppression testing for confirmation of autonomous aldosterone secretion. Postural testing, adrenal gland imaging, and adrenal venous sampling were also performed. Individuals affected by FH-II demonstrated lack of suppression of plasma A levels after 4 days of dexamethasone treatment (0.5 mg every 6 h). All patients had negative genetic testing for the defect associated with FH-I, the CYP11B1/CYP11B2 hybrid gene. Genetic linkage was then examined between FH-II and aldosterone synthase (the CYP11B2 gene) on chromosome 8q. A polyadenylase repeat within the 5'-region of the CYP11B2 gene and 9 other markers covering an approximately 80-centimorgan area on chromosome 8q21-8qtel were genotyped and analyzed for linkage. Two-point logarithm of odds scores were negative and ranged from -12.6 for the CYP11B2 polymorphic marker to -0.98 for the D8S527 marker at a recombination distance (theta) of 0. Multipoint logarithm of odds score analysis confirmed the exclusion of the chromosome 8q21-8qtel area as a region harboring the candidate gene for FH-II in this family. We conclude that FH-II shares autosomal dominant inheritance and hyperaldosteronism with FH-I, but, as demonstrated by the large kindred investigated in this report, it is clinically and genetically distinct. Linkage analysis demonstrated that the CYP11B2 gene is not responsible for FH-II in this family; furthermore, chromosome 8q21-8qtel most likely does not harbor the genetic defect in this kindred.     

Breast and ovarian cancer prone women and prophylactic surgery temptation

Aldosterone suppression by dexamethasone, and high 18-hydroxycortisol and 18-oxocortisol levels are used to differentiate glucocorticoid-remediable aldosteronism (GRA) from other forms of primary aldosteronism. These methods are time consuming, expensive, and impractical for large studies. Moreover, diagnosis of GRA requires a confirmatory genetic test. We evaluated 117 patients with primary aldosteronism referred to our centers by the use of a long PCR technique to reveal the chimeric gene of GRA. In 60 of 117 patients, the response of aldosterone to dexamethasone (2 mg/day for 4 days) was also assessed. None of our patients, including 2 pairs of siblings, was positive for the chimeric gene. The results of long PCR were confirmed by Southern blotting. Despite a negative genetic test, 6 patients (1 with aldosterone-producing adenoma and 5 with idiopathic hyperaldosteronism) had plasma aldosterone suppressed by dexamethasone (i.e. < or = 2 ng/dL). Of 117 patients, 43 were identified as having aldosterone-producing adenoma and 74 as having idiopathic hyperaldosteronism. In our experience, the long PCR technique is a reliable and simple test to at least exclude GRA in patients with primary aldosteronism. A short term dexamethasone suppression test of aldosterone can be misleading in identifying GRA. The prevalence of GRA in primary aldosteronism remains to be established.     

Malignant hypertension in a patient with primary aldosteronism with elevated active renin concentration

A 40-year-old male, with a past history of hypertension but receiving no medical treatment, was referred. He manifested malignant hypertension (190/130 mmHg; Keith-Wagener III), renal dysfunction (serum creatinine, 3.8 mg/dl), and elevated plasma aldosterone (450 pg/ml) and active renin concentration (ARC, 104 pg/ml). His blood pressure was controlled with multiple antihypertensive agents and ARC thus decreased (4.3 pg/ml), but aldosterone remained elevated. Abdominal magnetic resonance imaging (MRI) revealed a right adrenal adenoma, and aldosterone-producing adenoma was confirmed by adrenal venous sampling. Primary aldosteronism very rarely develops to malignant hypertension, and even in that case ARC is suppressed. Therefore this is a rare case of primary aldosteronism complicated with malignant hypertension and high ARC.     

Ultrasonographic study of adrenal gland tumors (report of 5 cases)

The authors study the ultrasound signs of the adrenal gland based on 5 different types of operated adrenal tumours (a lipoma, an adrenal cortical adenoma, a cyst, a corticoadrenaloma, an adrenal metastasis from a renal cell carcinoma). The ultrasonographic morphological criteria of the normal adrenal gland and each type of tumour are recalled and are illustrated by clinical cases. The value of ultrasonography in the investigation of this organ was evaluated in comparison with other imaging techniques. It constitutes a good first-line diagnostic guiding examination, but needs to be completed by other investigations (computed tomography, magnetic resonance imaging, etc.). Ultrasonography can also reveal asymptomatic adrenal tumours ("adrenal incidentalomas") in which the therapeutic decision (surveillance or surgery) must be based on criteria of size and appearance after a complete laboratory and morphological assessment.     

Preventive effects of superoxide dismutase derivatives modified with monosaccharides on reperfusion injury in rat liver transplantation

Focal nodular hyperplasia (FNH) and adenoma are rare benign hepatic tumors, and the standards for diagnosis and treatment still remain controversial. Usually adenoma is an indication for resection, due to its tendency to bleed and to degenerate; FNH, on the contrary, may be treated conservatively. Preoperation differential diagnosis is, however, difficult, often impossible. MATERIALS AND METHODS: Thirty-eight patients with presumed hepatic adenoma and/or FNH were studied at our department from 1984 to 1996. Preoperative assessment included clinical evaluation and symptoms, laboratory tests, liver biopsy, ultrasound scan, computed tomography scan, magnetic resonance imaging, scintigraphy, and angiography. Thirteen patients had a presumed diagnosis of FNH, 16 of adenoma, and 9 of undetermined benign lesions; 27 had hepatic resections (3 with laparoscopic technique), and 11 were not operated on and are actually under a strict follow-up observation. RESULTS: The final diagnosis was 19 FNH and 19 adenomas (2 of which contained areas of hepatocarcinoma). Presumed diagnosis was confirmed in 71% of cases. Use of oral contraceptives, abdominal symptoms, and pathologic liver test results were frequent in patients with adenomas. There were no deaths after surgery. All resected patients were tumor free during the follow-up, and in 10 of the 11 nonoperated cases, the size of the nodules remained unchanged. We conclude that precise diagnosis of these benign liver tumors remains difficult and sometimes impossible, despite new imaging techniques. Hepatic resections can be performed under very safe conditions; laparoscopic surgery may play a role in selected cases. Adenomas and uncertain cases are clear indications for surgery. Only when a diagnosis of FNH can be firmly confirmed in asymptomatic patients is strict observation without surgery recommended.     

Laceration of a benign adrenal adenoma mimicking a splenic rupture

Lacerations of adrenal tumors are very rare events and have been described for myelolipoma, pheochromocytoma, and cortisol-producing adenoma. We report on a patient who was admitted with suspected splenic rupture. Computed tomography showed a mass 14 cm in diameter adjacent to the spleen, but selective angiography revealed blood supply by the left suprarenal artery. A ruptured adrenal tumor was therefore diagnosed and resected. No hormone production was detected. Histologically a benign adrenal adenoma was found. Frequency, diagnosis and therapy of adrenal masses are discussed.     

Carcinosarcoma of the adrenal cortex presenting with mineralocorticoid excess

An adrenal carcinosarcoma is reported in a 79-year-old woman presenting with clinical signs of hyperaldosteronism. The tumor weighed 199 g and consisted of areas typical of adrenal carcinoma and areas of sarcoma. The sarcomatous component of the tumor showed osteogenic and chondroid differentiation. Vimentin stained both the carcinomatous and sarcomatous regions. Four months after resection, the patient developed metastases. This is the third reported case of adrenal carcinosarcoma and the only case in which hyperaldosteronism or bony differentiation was observed.